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Peggy Gravel, a neurotic, delusional, suburban housewife, and her overweight maid, Grizelda Brown, go on the lam after Grizelda smothers Peggy's husband, Bosley, to death. The two are arrested by a cross-dressing policeman who gives them an ultimatum: go to jail or be exiled to Mortville, a filthy shantytown ruled by the evil Queen Carlotta and her treasonous daughter, Princess Coo-Coo.

Peggy and Grizelda choose Mortville, but still engage in lesbian prison sex. They become associates of self-hating lesbianwrestler Mole McHenry, who wants a sex change to please her lover, Muffy St. Jacques. Most of Mortville's social outcasts—criminals, nudists, and sexual deviants—conspire to overthrow Queen Carlotta, who banishes her daughter, Coo-Coo, after she elopes with a garbage collector, who is later shot to death by the guards. Coo-Coo hides in Peggy and Grizelda's house with her dead lover. When Peggy betrays Coo-Coo to the Queen's guards, Grizelda fights them, and dies when the house collapses on her. Peggy, however, joins the queen in terrorizing her subjects, even infecting them (and Princess Coo-Coo) with rabies.

Eventually, Mortville's denizens, led by Mole, overthrow Queen Carlotta and execute Peggy by shooting a gun up her anus. To celebrate their freedom, the townsfolk roast Carlotta on a spit and serve her, pig-like, on a platter with an apple in her mouth.

Desperate Living was edited for ten weeks in the basement of editor Charles Roggero's home. It was Waters' first film with original music, by Chris Lobingier and Allen Yanus to provide a "cheesy Doctor Zhivago-type score".[4][page needed]

Desperate Living is the only feature film Waters made without Divine prior to the actor's death in 1988. Divine had to reluctantly back away from the film because he was committed to appearing in The Neon Woman. Susan Lowe, who had appeared in small or supporting roles in Waters' previous films, was chosen to take over for the role of Mole McHenry. This was also Waters' first film without David Lochary, the reason for which being Lochary's addiction to drugs. Waters said "The reason that David wasn't in Desperate Living is because of PCP. That's all that's to it. I know that's why he wasn't in the film, and he knows it too." Lochary would later die of a drug overdose during the film's production.

Waters had received a copy of Liz Renay's autobiographyMy Face for the World to See and wanted to offer her a role in the film. He went to see Renay in a burlesque show in Boston, then traveled to Los Angeles to offer her the role of Muffy St. Jacques. He offered her only a brief outline of the story, withholding some of the more graphic details for fear that she might refuse the role. Renay accepted the offer and flew to Baltimore for three weeks of shooting (which was, reportedly, all that the production could afford to pay Renay for her services).[5][page needed]

As with Waters' previous films, the premiere was held in the auditorium of the University of Baltimore. There was a brief controversy when lesbian groups attacked the film for its depiction of lesbianism, and for taking the title of a defunct pro-lesbian magazine. New Line Cinema blew the film up from 16mm to 35mm and opened it at midnight in Manhattan, though the original poster (featuring a cooked rat on a plate) was rejected by The New York Times to run, forcing a new poster to be created three days before the opening. The new poster featured Liz Renay in a screaming pose, fashioned from a production still.

Critics from Good Housekeeping walked out of the film after ten minutes. Otherwise, Playboy enjoyed the film, stating it had to be "seen to be believed". David Chute of The Boston Phoenix said of the film: "In Desperate Living, Waters comes close to creating a work of true trash art." The film currently holds a 70% rating on Rotten Tomatoes.[6]

The sound of a ringing telephone is then heard on a loop before, at the very end of the track, a message from the Marilyn Manson Family Intervention Hotline answering machine is heard, specifically a mother asking for her son's name to be removed from the band's mailing list.

The musical Miss Saigon features a musical scene with the first words being "Coo-Coo Princess".